Proton pump inhibitors for clopidogrel patients ‘not so dangerous’

By Piriya Mahendra

The interaction between proton pump inhibitors and clopidogrel is "clinically unimportant," say researchers in the BMJ.

Ian Douglas (London School of Hygiene and Tropical Medicine London, UK) and co-workers found that in a self-controlled case series analysis, to remove the effect of differences between people, there was no association between proton pump inhibitor use and myocardial infarction (MI) in patients prescribed clopidogrel and aspirin.

Moreover, there was no association with MI for other 2C19 inhibitors - fluoxetine and paroxetine - or non-2C19 inhibitors - citalopram and ranitidine - in these patients.

"The use of a proton pump inhibitor with clopidogrel and aspirin is well proved to prevent harm through gastrointestinal bleeding, and we should continue to consider proton pump inhibitors as important prophylactic drugs in patients at high risk," the authors write.

Of the 24,471 patients prescribed clopidogrel and aspirin who were included in the study, 12,439 (50%) were also prescribed a proton pump inhibitor at some point.

Death or MI occurred in 1419 (11%) patients while they received a proton pump inhibitor compared with 1341 (8%) patients who did not receive one.

Multivariate analysis showed that the hazard ratio for the association between proton pump inhibitor use and death or incident MI was 1.37.

Similar results were seen when the authors looked at the secondary outcomes of the study ‑ death, incident MI, vascular death, and nonvascular death - with exposure to drugs other than proton pump inhibitors that would not be expected to interact with clopidogrel.

Indeed, the results were comparable between other 2C19 inhibitors and non-2C19 inhibitors for these outcomes, at hazard ratios ranging from 1.13 to 1.73, and 1.14 to 1.84, respectively.

"These observed associations… suggest these results could be driven by important differences between proton pump inhibitor users and nonusers rather than showing a causal association," the authors remark.

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